Hypercholesterolemia is known as a major risk factor against ischemic heart disease such as arteriosclerosis. Bile acid sequestrants have been utilized to treat these diseases. However, this therapy seldom satisfies all the needs even if it seems effective. This drug should be administered in a large amount, namely several g doses per once.
Presently, lovastatin and its homologous compound, simvastatin are commercially available as highly active therapeutic agents for anti-hypercholesterolemia. They suppress HMG-CoA reductase, by which the cholesterol biosynthesis is inhibited. These compounds so-called statins are reported to exist in a dihydroxylic acid form with an open circular structure as depicted in formular 2 and in a lactone form as depicted in formular 1. 
Wherein Z is hydrogen, ammonium or metal cation, R is a radical of formular 3 and R1 is H or CH3. 
Statins are known to be active in a dihydroxylic acid form physiologically, but usually administered in a lactone form for patients. Therefore, it is necessary to develop an efficient method to perform a lactonization in a high productive yield. Since the lactonization is an equilibriated process, specific means should be utilized to transfer the equilibrium toward lactones as shown in reaction formular 1 in order to produce lactonized products in a high yield.dihydroxylic acid (or ammonium salt)lactone+H2O(+NH3)  <Reaction Formular 1>
In U.S. Pat. No. 4,820,850, azeotropic distillation or nitrogen sweep were exploited to complete the lactonization by removing by-products of the reaction (water or ammonia) from reacted mixtures. However, there are several disadvantages. That is to say, it is generally refluxed under toluene solvent and should be heated at a high temperature (110° C.). Under such as high temperature, lactonized product cause inter-reaction between them, and results in increasing the amount of heterodimers as depicted in formula 1a. 
Wherein, R and R1 are defined as described above.
At this moment, the content of heterodimers reaches about 0.4% typically. This heterodimer is difficult to be purified from targeting lactone products, even if very precise recrystallization technique is applied. Practically, in case that these kinds of heterodimers are present, the total productive yield and the purity of lactone products are decreased. Therefore, the reaction mixture is diluted in a high degree before using in order to minimize the formation of heterodimers. However, this is also disadvantageous to the efficiency of the reaction.
Furthermore, Korean Patent Publication No. 97-11286 (U.S. Pat. No. 4,916,239) has disclosed another process for preparing lactones, in which the organic solvent mixed with water and having a solubility different enough between hydroxylate and lactone was utilized. Concretely, the separated hydroxylates of mevinic acid or its homologous compounds or the derivatives of ammonium salts or metal salts were reacted with one adopted among acetic acid, a mediator and strong acid catalysts and then an equilibrium between the separated hydroxylate and the lactone was formed. Afterward, water was added in a sufficient amount so as to crystallize the lactone completely. Unfortunately, in this method strong acids such as methanesulfonic acid, chloric acid, sulfuric acid, trifluoroacetic acid and the like should be utilized at the range of 1.2˜1.5 M and strong bases also be added in a large amount to neutralize the solution. Therefore, this is not available for the industrial application in a large scale as well as very harmful environmentally. Besides, extra water should be blended in order to complete the lactonization, but this induces crystallization again onto the existing crystal, and become non-homogeneous. In addition, there are some other problems. The process might not be effective, since the resulting product be not filtrated thoroughly. Then, the procedure for the reaction and the work-up takes a very long time in the range of 9˜12 hours, which reduces the productive yield. Furthermore, the resulting lactone product prepared by the above method still have heterodimers in less than 0.2%, typically in about 0.15%.
In order to improve the conventional method described above, U.S. Pat. No. 5,917,058 has illustrated the process for the preparing lactones, in which dihydroxy groups of statins or its homologous compounds, especially in an ammonium salt form, are reacted with acetic acid medium without an extra acidic catalyst and additional removing steps of water or ammonia, at 35˜40° C. After that, insoluble solvent including water, hexane, cyclohexane or the like is added to produce lactones. However, in this method acetic acid as a solvent is utilized in 3˜7-fold larger amounts than that of the reactant and should be neutralized with bases, and the neutral salt (ammonium acetate) is produced and remained in the final lactone compounds. Therefore, another process is required to recrystallize, which is inconvenient and uneconomical. The lactone compound and its neutral salts exist in a mixed state and are not filtrated properly, and the process for the preparation becomes inefficient. Furthermore, extra contaminant formed from the 3-hydroxy group of cyclolactone circle through dehydration can be observed in an acidic condition under a heated state, since only acetic acid is used as a solvent. This contaminant is not removed easily even by the recrystalization and might decrease the purity and the productive yield of lactone compounds.
Thus, U.S. Pat. No. 4,916,239 and No. 5,917,058 have disclosed that the lactonization be performed at a low temperature on account of organic or inorganic acid, however it is limited to reduce the heterodimers in the amount. Once the lactonization was accomplished, it is impossible to reduce heterodimer, since basically H+ ion present in the reactant is reacted with the carbonyl group of lactone circle and makes heterodimers with other lactone products.
As demonstrated above, it is necessary to develop a new process for preparing lactone compounds in a high purity. Precisely, since lactone compounds are prepared in an equilibriated reaction from mevinic acid or its homologous compounds, the by-product (water and ammonia) might be removed from the reacted mixture so that the process for the preparation is completed. Through this procedure, the lactone compound is obtained in a high yield and the resulting heterodimers are reduced in the amount.